Open AccessC‐Cbl regulates c‐MPL receptor trafficking and its internalization
Author(s) -
Märklin Melanie,
Tandler Claudia,
Kopp HansGeorg,
Hoehn Kyle L.,
QuintanillaMartinez Leticia,
Borst Oliver,
Müller Martin R.,
Saur Sebastian J.
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15785
Subject(s) - internalization , thrombopoietin , thrombopoiesis , megakaryocyte , microbiology and biotechnology , platelet , ubiquitin ligase , receptor , conditional gene knockout , chemistry , biology , ubiquitin , progenitor cell , haematopoiesis , cancer research , immunology , stem cell , gene , biochemistry , phenotype
Thrombocyte formation from megakaryocyte and their progenitor cells is tightly regulated by thrombopoietin (TPO) and its receptor c‐MPL, thereby maintaining physiological functionality and numbers of circulating platelets. In patients, dysfunction of this regulation could cause thrombocytopenia or myeloproliferative syndromes. Since regulation of this pathway is still not completely understood, we investigated the role of the ubiquitin ligase c‐Cbl which was previously shown to negatively regulated c‐MPL signalling. We developed a new conditional mouse model using c‐Cbl fl/fl Pf4 Cre mice and demonstrated that platelet‐specific knockout of c‐Cbl led to severe microthrombocytosis and impaired uptake of TPO and c‐MPL receptor internalization. Furthermore, we characterized a constitutive STAT5 activation c‐Cbl KO platelets. This study identified c‐Cbl as a potential player in causing megakaryocytic and thrombocytic disorders.